The overall objective of this project is to investigate the metabolism and biochemical actions of cadmium in mammalian biochemical systems in a effort to understand parameters associated with cadmium toxicity. During this phase of the project the following will be investigated: a) The mechanism of hepatic metallothionein biosynthesis. Polysomal and postribosomal poly(A)mRNA will be translated in a wheat germ system and newly synthesized metallothionein will be measured. mRNA will be obtained from cadium-fed and cadmium-injected rats and from isolated rat liver parenchymal cells in primary culture previously exposed to various treatments. Methallothinonein mRNA will be purifed ad the cDNA prepared to measure this mRNA. These data will be related to cadmium content of liver cells. b) The mechanism of renal metallothionein biosynthesis. The rate of synthesis will be measured in rat kidney after injections and oral administration of cadmium. Polysomal and postribosomal poly(A)mRNA will be translated in a wheat germ system and newly synthesized metallothionein will be measured and related to the rate of synthesis. The cDNA will be prepared from kidney metallothionein mRNA and used as a probe to relate this mRNA to cadmium accumulation and metallothionein in kidney. c) The mechanisms of intestinal cadmium absorption will be investigated using a vascularly perfused rat intestine. The influences of various agents on the uptake of cadmium into mucosal cells and then transfer of cadmium to the vascular supply (plasma) will be examined. Cadmium transport will be examined with brush border membrane vesicles derived from rat intestine.